tbuckley/cabot-search huggingface dataset:
Reply: Artificial cycle frozen embryo transfer and obstetric adverse outcomes: association or causation?
Authors: T R Zaat, F Mol, M van Wely
Journal: Human Reproduction Update (2023)

Journal Article Reply: Artificial cycle frozen embryo transfer and obstetric adverse outcomes: association or causation? Get access T R Zaat, T R Zaat Center for Reproductive Medicine, Amsterdam UMC, location Amsterdam Medical Center, Amsterdam, The NetherlandsAmsterdam Reproduction and Development Research Institute, Amsterdam UMC, Amsterdam, The Netherlands Search for other works by this author on: Oxford Academic PubMed Google Scholar F Mol, F Mol Center for Reproductive Medicine, Amsterdam UMC, location Amsterdam Medical Center, Amsterdam, The NetherlandsAmsterdam Reproduction and Development Research Institute, Amsterdam UMC, Amsterdam, The Netherlands Search for other works by this author on: Oxford Academic PubMed Google Scholar M van Wely M van Wely Center for Reproductive Medicine, Amsterdam UMC, location Amsterdam Medical Center, Amsterdam, The NetherlandsAmsterdam Reproduction and Development Research Institute, Amsterdam UMC, Amsterdam, The Netherlands Correspondence address. Center for Reproductive Medicine, Amsterdam UMC, location Amsterdam Medical Center, Meibergdreef 9, Amsterdam, The Netherlands. Tel: +31-(0)20-566-3557; E-mail: m.vanwely@amsterdamumc.nl https://orcid.org/0000-0001-8263-213X Search for other works by this author on: Oxford Academic PubMed Google Scholar Human Reproduction Update, dmad021, https://doi.org/10.1093/humupd/dmad021 Published: 28 July 2023 Article history Editorial decision: 12 July 2023 Received: 12 July 2023 Published: 28 July 2023
Orthogonal Gelations to Synthesize Core–Shell Hydrogels Loaded with Nanoemulsion‐Templated Drug Nanoparticles for Versatile Oral Drug Delivery
Authors: Lucas Attia, Liang‐Hsun Chen, Patrick S. Doyle
Journal: Advanced Healthcare Materials (2023)

Abstract Hydrophobic active pharmaceutical ingredients (APIs) are ubiquitous in the drug development pipeline, but their poor bioavailability often prevents their translation into drug products. Industrial processes to formulate hydrophobic APIs are expensive, difficult to optimize, and not flexible enough to incorporate customizable drug release profiles into drug products. Here, a novel, dual‐responsive gelation process that exploits orthogonal thermo‐responsive and ion‐responsive gelations is introduced. This one‐step “dual gelation” synthesizes core–shell (methylcellulose‐alginate) hydrogel particles and encapsulates drug‐laden nanoemulsions in the hydrogel matrices. In situ crystallization templates drug nanocrystals inside the polymeric core, while a kinetically stable amorphous solid dispersion is templated in the shell. Drug release is explored as a function of particle geometry, and programmable release is demonstrated for various therapeutic applications including delayed pulsatile release and sequential release of a model fixed‐dose combination drug product of ibuprofen and fenofibrate. Independent control over drug loading between the shell and the core is demonstrated. This formulation approach is shown to be a flexible process to develop drug products with biocompatible materials, facile synthesis, and precise drug release performance. This work suggests and applies a novel method to leverage orthogonal gel chemistries to generate functional core–shell hydrogel particles.
Reply to Li <i>et al.</i> and to Bhattacharya <i>et al.</i>
Authors: Shaurya Taran, Camilo Diaz-Cruz, Sung-Min Cho, Robert D. Stevens
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"Reply to: The Effectiveness of Prophylactic Use of HFNC and NIPPV on Reintubation: Concerning the Heterogeneity of ABI Patients." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.
Fiber Microarchitecture in Interpenetrating Collagen–Alginate Hydrogel with Tunable Mechanical Plasticity Regulates Tumor Cell Migration
Authors: Zhao Wei, Jingyi Liu, Yuanbo Jia, Meng Lei, Songbai Zhang, Pan Xi, Yufei Ma, Min Zhang, Jinlu Ma, Lin Wang, Hui Guo, Feng Xu
Journal: Advanced Healthcare Materials (2023)

The fiber structures of tumor microenvironment (TME) are well-known in regulating tumor cell behaviors, and the plastic remolding of TME has recently been suggested to enhance tumor metastasis as well. However, the interrelationship between the fiber microarchitecture and matrix plasticity is inextricable by existing in vitro models. The individual roles of fiber microarchitecture and matrix plasticity in tuning tumor cell behaviors remain elusive. This study develops an interpenetrating collagen-alginate hydrogel platform with independently tunable matrix plasticity and fiber microarchitecture through an interpenetrating strategy of alginate networks and collagen I networks. With this hydrogel platform, it is demonstrated that tumor cells in high plasticity hydrogels are more extensive and aggressive than in low plasticity hydrogels and fiber structures only have influence in high plasticity hydrogels. The study further elucidates the underlying mechanisms through analyzing the distribution of forces within the matrix and tracking the focal adhesions (FAs) and finds that highly plastic hydrogels can activate the FAs formation, whereas the maturation and stability of FAs are dominated by fiber dispersion. This study not only establishes new ideas on how cells interact with TME cues but also would help to further finely tailor engineered hydrogel platforms for studying tumor behaviors in vitro.
The Effectiveness of Prophylactic Use of High-Flow Nasal Cannula Oxygen Therapy and Noninvasive Positive Pressure Ventilation on Reintubation: Concerning the Heterogeneity of Patients with Acute Brain Injury
Authors: Hong Peng Li, Ya Ru Yan, Qing Yun Li
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"The Effectiveness of Prophylactic Use of HFNC and NIPPV on Reintubation: Concerning the Heterogeneity of ABI Patients." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.
When I use a word . . . Coroners’ duties: enquiry and prevention
Authors: Jeffrey K Aronson
Journal: BMJ (2023)

The Coroner’s Rules 1984 included Rule 43, titled “Prevention of future fatalities.” The rule stated that “A coroner who believes that action should be taken to prevent the recurrence of fatalities similar to that in respect of which the inquest is being held may announce at the inquest that he is reporting the matter in writing to the person or authority who may have power to take such action and he may report the matter accordingly.” Rule 43 was strengthened in 2009 by The Coroners and Justice Act and in 2013 by The Coroners (Investigations) Regulations. The reports are now called Section 28 reports or Prevent Future Deaths reports (PFDs). The legislation established the principle that if a coroner undertaking an investigation into an individual9s death identifies circumstances that give rise to a concern that there are risks that other deaths will occur as a result, and is of the opinion that action should be taken to prevent the occurrence or continuation of such circumstances, or to eliminate or reduce the risks of such deaths, the coroner must report the matter to anyone who, in the coroner’s opinion, may be able to take or initiate such action. The word “may” in 1984 became “must” in 2009. Anyone who receives such a report must, again “must,” reply within 56 days, giving details of any action that has been taken or proposed or explaining why no action is proposed. However, relatively few PFDs are written compared with the number of inquests carried out, and even fewer responses are received.
Prevalence and significance of <i>DDX41</i> gene variants in the general population
Authors: Sruthi Cheloor Kovilakam, Muxin Gu, William G. Dunn, Ludovica Marando, Clea Barcena, Serena Nik-Zainal, Irina Mohorianu, Siddhartha P. Kar, Margarete A. Fabre, Pedro M. Quiros, George S. Vassiliou
Journal: Blood (2023)

Germ line variants in the DDX41 gene have been linked to myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) development. However, the risks associated with different variants remain unknown, as do the basis of their leukemogenic properties, impact on steady-state hematopoiesis, and links to other cancers. Here, we investigate the frequency and significance of DDX41 variants in 454 792 United Kingdom Biobank (UKB) participants and identify 452 unique nonsynonymous DNA variants in 3538 (1/129) individuals. Many were novel, and the prevalence of most varied markedly by ancestry. Among the 1059 individuals with germ line pathogenic variants (DDX41-GPV) 34 developed MDS/AML (odds ratio, 12.3 vs noncarriers). Of these, 7 of 218 had start-lost, 22 of 584 had truncating, and 5 of 257 had missense (odds ratios: 12.9, 15.1, and 7.5, respectively). Using multivariate logistic regression, we found significant associations of DDX41-GPV with MDS, AML, and family history of leukemia but not lymphoma, myeloproliferative neoplasms, or other cancers. We also report that DDX41-GPV carriers do not have an increased prevalence of clonal hematopoiesis (CH). In fact, CH was significantly more common before sporadic vs DDX41-mutant MDS/AML, revealing distinct evolutionary paths. Furthermore, somatic mutation rates did not differ between sporadic and DDX41-mutant AML genomes, ruling out genomic instability as a driver of the latter. Finally, we found that higher mean red cell volume (MCV) and somatic DDX41 mutations in blood DNA identify DDX41-GPV carriers at increased MDS/AML risk. Collectively, our findings give new insights into the prevalence and cognate risks associated with DDX41 variants, as well as the clonal evolution and early detection of DDX41-mutant MDS/AML.
Type 1 Diabetes Genetic Risk Score Differentiates Subgroups of Ketosis-Prone Diabetes
Authors: Deborah Osafehinti, Surya N. Mulukutla, Christiane S. Hampe, Ruchi Gaba, Nalini Ram, Michael N. Weedon, Richard A. Oram, Ashok Balasubramanyam
Journal: Diabetes Care (2023)

To determine whether genetic risk for type 1 diabetes (T1D) differentiates the four Aβ subgroups of ketosis-prone diabetes (KPD), where A+ and A- define the presence or absence of islet autoantibodies and β+ and β- define the presence or absence of β-cell function.
Low-density lipoprotein promotes microvascular thrombosis by enhancing von Willebrand factor self-association
Authors: Dominic W. Chung, Kimsey Platten, Koya Ozawa, Reheman Adili, Nathalie Pamir, Forrest Nussdorfer, Alexander St. John, Minhua Ling, Jennie Le, Jeff Harris, Nicole Rhoads, Yi Wang, Xiaoyun Fu, Junmei Chen, Sergio Fazio, Jonathan R. Lindner, José A. López
Journal: Blood (2023)

von Willebrand factor (VWF) mediates primary hemostasis and thrombosis in response to hydrodynamic forces. We previously showed that high shear promoted self-association of VWF into hyperadhesive strands, which can be attenuated by high-density lipoprotein (HDL) and apolipoprotein A-I. In this study, we show that low-density lipoprotein (LDL) binds VWF under shear and enhances self-association. Vortexing VWF in tubes resulted in its loss from the solution and deposition onto tube surfaces, which was prevented by HDL. At a stabilizing HDL concentration of 1.2 mg/mL, increasing concentrations of LDL progressively increased VWF loss, the effect correlating with the LDL-to-HDL ratio and not the absolute concentration of the lipoproteins. Similarly, HDL diminished deposition of VWF in a post-in-channel microfluidic device, whereas LDL increased both the rate and extent of strand deposition, with both purified VWF and plasma. Hypercholesterolemic human plasma also displayed accelerated VWF accumulation in the microfluidic device. The initial rate of accumulation correlated linearly with the LDL-to-HDL ratio. In Adamts13-/- and Adamts13-/-LDLR-/- mice, high LDL levels enhanced VWF and platelet adhesion to the myocardial microvasculature, reducing cardiac perfusion, impairing systolic function, and producing early signs of cardiomyopathy. In wild-type mice, high plasma LDL concentrations also increased the size and persistence of VWF-platelet thrombi in ionophore-treated mesenteric microvessels, exceeding the accumulation seen in similarly treated ADAMTS13-deficient mice that did not receive LDL infusion. We propose that targeting the interaction of VWF with itself and with LDL may improve the course of thrombotic microangiopathies, atherosclerosis, and other disorders with defective microvascular circulation.
Contribution of MEK Inhibition to BRAF/MEK Inhibitor Combination Treatment of <i>BRAF</i>-Mutant Melanoma: Part 2 of the Randomized, Open-Label, Phase III COLUMBUS Trial
Authors: Paolo A. Ascierto, Reinhard Dummer, Helen J. Gogas, Ana Arance, Mario Mandala, Gabriella Liszkay, Claus Garbe, Dirk Schadendorf, Ivana Krajsova, Ralf Gutzmer, Vanna Chiarion-Sileni, Caroline Dutriaux, Jan Willem B. de Groot, Naoya Yamazaki, Carmen Loquai, Caroline Robert, Keith T. Flaherty
Journal: Journal of Clinical Oncology (2023)

In COLUMBUS part 1, patients with advanced BRAFV600-mutant melanoma were randomly assigned 1:1:1 to encorafenib 450 mg once daily plus binimetinib 45 mg twice a day (COMBO450), vemurafenib 960 mg twice a day, or encorafenib 300 mg once daily (ENCO300). As previously reported, COMBO450 improved progression-free survival (PFS) versus vemurafenib (part 1 primary end point) and ENCO300 (part 1 key secondary end point; not statistically significant). Part 2, requested by the US Food and Drug Administration, evaluated the contribution of binimetinib by maintaining the same encorafenib dosage in the combination (encorafenib 300 mg once daily plus binimetinib 45 mg twice daily [COMBO300]) and ENCO300 arms.In part 2, patients were randomly assigned 3:1 to COMBO300 or ENCO300. ENCO300 (parts 1 and 2) data were combined, per protocol, for PFS analysis (key secondary end point) by a blinded independent review committee (BIRC). Other analyses included overall response rate (ORR), overall survival, and safety.Two hundred fifty-eight patients received COMBO300, and 86 received ENCO300. Per protocol, ENCO300 arms (parts 1 and 2 combined) were also evaluated (n = 280). The median follow-up for ENCO300 was 40.8 months (part 1) and 57.1 months (part 2). The median PFS (95% CI) was 12.9 months (10.9 to 14.9) for COMBO300 versus 9.2 months (7.4 to 11.1) for ENCO300 (parts 1 and 2) and 7.4 months (5.6 to 9.2) for ENCO300 (part 2). The hazard ratio (95% CI) for COMBO300 was 0.74 (0.60 to 0.92; two-sided P = .003) versus ENCO300 (parts 1 and 2). The ORR by BIRC (95% CI) was 68% (62 to 74) and 51% (45 to 57) for COMBO300 and ENCO300 (parts 1 and 2), respectively. COMBO300 had greater relative dose intensity and fewer grade 3/4 adverse events than ENCO300.COMBO300 improved PFS, ORR, and tolerability compared with ENCO300, confirming the contribution of binimetinib to efficacy and safety.
Cryo-EM structures of human arachidonate 12S-lipoxygenase bound to endogenous and exogenous inhibitors
Authors: Jesse I. Mobbs, Katrina A. Black, Michelle Tran, Wessel A. C. Burger, Hariprasad Venugopal, Theodore R. Holman, Michael Holinstat, David M. Thal, Alisa Glukhova
Journal: Blood (2023)
Lenalidomide and dexamethasone maintenance with or without ixazomib, tailored by residual disease status in myeloma
Authors: Laura Rosiñol, Albert Oriol, Rafael Ríos, María Jesús Blanchard, Isidro Jarque, Joan Bargay, Miguel Teodoro Hernández, Valentín Cabañas, Estrella Carrillo-Cruz, Anna Sureda, Joaquín Martínez-López, Isabel Krsnik, Maria Esther González, Luis Felipe Casado, Josep María Martí, Cristina Encinas, Felipe de Arriba, Luis Palomera, Antonia Sampol, Yolanda González-Montes, Elena Cabezudo, Bruno Paiva, Noemí Puig, María Teresa Cedena, Javier de la Cruz, María-Victoria Mateos, Jesús San Miguel, Juan José Lahuerta, Joan Bladé
Journal: Blood (2023)
ROSEWOOD: A Phase II Randomized Study of Zanubrutinib Plus Obinutuzumab Versus Obinutuzumab Monotherapy in Patients With Relapsed or Refractory Follicular Lymphoma
Authors: Pier Luigi Zinzani, Jiří Mayer, Christopher R. Flowers, Fontanet Bijou, Ana C. De Oliveira, Yuqin Song, Qingyuan Zhang, Michele Merli, Krimo Bouabdallah, Peter Ganly, Huilai Zhang, Roderick Johnson, Alejandro Martín García-Sancho, Mariano Provencio Pulla, Marek Trněný, Sam Yuen, Herve Tilly, Edwin Kingsley, Gayane Tumyan, Sarit E. Assouline, Rebecca Auer, Elena Ivanova, Pil Kim, Sha Huang, Richard Delarue, Judith Trotman
Journal: Journal of Clinical Oncology (2023)

Deep and durable responses with zanubrutinib plus obinutuzumab in patients with R/R FL.
When Treatment Pressures Become Coercive: A Context-Sensitive Model of Informal Coercion in Mental Healthcare
Authors: Christin Hempeler, Esther Braun, Sarah Potthoff, Jakov Gather, Matthé Scholten
Journal: The American Journal of Bioethics (2023)

Treatment pressures are communicative strategies that mental health professionals use to influence the decision-making of mental health service users and improve their adherence to recommended treatment. Szmukler and Appelbaum describe a spectrum of treatment pressures, which encompasses persuasion, interpersonal leverage, offers and threats, arguing that only a particular type of threat amounts to informal coercion. We contend that this account of informal coercion is insufficiently sensitive to context and fails to recognize the fundamental power imbalance in mental healthcare. Based on a set of counterexamples, we argue that what makes a proposal coercive is not whether service users will actually be made worse off if they reject the proposal, but rather whether they have the justified belief that this is the case. Whether this belief is justified depends on the presence of certain contextual factors, such as strong dependency on professionals and the salient possibility of formal coercion.
Nationwide Assessment of Patient Trajectories in Mantle Cell Lymphoma: The Swedish MCLcomplete Project
Authors: Mats Jerkeman, Sara Ekberg, Ingrid Glimelius, Alexandra Albertsson-Lindblad, Joshua P. Entrop, Fredrik Ellin, Kristina Sonnevi, Catharina Lewerin, Lena Brandefors, Karin E. Smedby
Journal: HemaSphere (2023)

Mantle cell lymphoma (MCL) is a B-cell malignancy currently considered incurable. Although some patients obtain prolonged remission after first-line chemoimmunotherapy, many will need several treatment lines. Here, we present a nationwide assessment of treatment strategies, time to progression and survival in MCL. All patients diagnosed with MCL 2006–2018 were identified in the Swedish Lymphoma Register. Information on all lines of therapy was extracted from the medical records. Overall and progression-free survival (OS and PFS) were assessed through August 2021. In total, 1367 patients were included (median age, 71 years) and median follow-up was 6.8 years. Two hundred and one (15%) were managed initially with watch-and-wait, but 1235 (90%) eventually received treatment. The most frequently used first-line regimens were rituximab-bendamustine (BR) (n = 368; 30%) and Nordic MCL2 (n = 342; 28%). During follow-up, 630 patients (46%) experienced relapse/progression and 546 (40%) received second-line treatment. The most frequently used second-line regimen was BR (n = 185; 34%) but otherwise a wide variety of second-line treatments were used. Further, 382 and 228 patients experienced a second or third relapse/progression, respectively. Median PFS after first (PFS-1), second (PFS-2), third (PFS-3), and fourth (PFS-4) treatment lines was 29.4, 8.9, 4.3, and 2.7 months. Patients with early progression, defined as a PFS-1 &lt;24 months, had an inferior median OS of 13 versus 37 months in patients with later relapse. For patients treated with frontline BR, however, time to relapse had no impact on later outcome. By use of nationwide population-based data, we provide important benchmarks for future studies of all treatment lines in MCL.
High-Throughput Screening to Advance In Vitro Toxicology: Accomplishments, Challenges, and Future Directions
Authors: Caitlin Lynch, Srilatha Sakamuru, Masato Ooka, Ruili Huang, Carleen Klumpp-Thomas, Paul Shinn, David Gerhold, Anna Rossoshek, Sam Michael, Warren Casey, Michael F. Santillo, Suzanne Fitzpatrick, Russell S. Thomas, Anton Simeonov, Menghang Xia
Journal: The Annual Review of Pharmacology and Toxicology (2023)

Traditionally, chemical toxicity is determined by in vivo animal studies, which are low throughput, expensive, and sometimes fail to predict compound toxicity in humans. Due to the increasing number of chemicals in use and the high rate of drug candidate failure due to toxicity, it is imperative to develop in vitro, high-throughput screening methods to determine toxicity. The Tox21 program, a unique research consortium of federal public health agencies, was established to address and identify toxicity concerns in a high-throughput, concentration-responsive manner using a battery of in vitro assays. In this article, we review the advancements in high-throughput robotic screening methodology and informatics processes to enable the generation of toxicological data, and their impact on the field; further, we discuss the future of assessing environmental toxicity utilizing efficient and scalable methods that better represent the corresponding biological and toxicodynamic processes in humans.
LP(a): Structure, Genetics, Associated Cardiovascular Risk, and Emerging Therapeutics
Authors: Erfan Tasdighi, Rishav Adhikari, Omar Almaadawy, Thorsten M. Leucker, Michael J. Blaha
Journal: The Annual Review of Pharmacology and Toxicology (2023)

Lipoprotein(a) [Lp(a)] is a molecule bound to apolipoprotein(a) with some similarity to low-density lipoprotein cholesterol (LDL-C), which has been found to be a risk factor for cardiovascular disease (CVD). Lp(a) appears to induce inflammation, atherogenesis, and thrombosis. Approximately 20% of the world's population has increased Lp(a) levels, determined predominantly by genetics. Current clinical practices for the management of dyslipidemia are ineffective in lowering Lp(a) levels. Evolving RNA-based therapeutics, such as the antisense oligonucleotide pelacarsen and small interfering RNA olpasiran, have shown promising results in reducing Lp(a) levels. Phase III pivotal cardiovascular outcome trials [Lp(a)HORIZON and OCEAN(a)] are ongoing to evaluate their efficacy in secondary prevention of major cardiovascular events in patients with elevated Lp(a). The future of cardiovascular residual risk reduction may transition to a personalized approach where further lowering of either LDL-C, triglycerides, or Lp(a) is selected after high-intensity statin therapy based on the individual risk profile and preferences of each patient.
WT1 and PRAME RNA-loaded dendritic cell vaccine as maintenance therapy in de novo AML after intensive induction chemotherapy
Authors: Yngvar Fløisand, Mats Remberger, Iris Bigalke, Dag Josefsen, Helen Vålerhaugen, Else Marit Inderberg, Richard W. Olaussen, Bjørn Tore Gjertsen, Rene Goedkoop, Christiane Geiger, Petra U. Prinz, Frauke M. Schnorfeil, Kai Pinkernell, Dolores J. Schendel, Gunnar Kvalheim
Journal: Leukemia (2023)